This proposal is a response to NEI Program Announcement on Cannabinoids in the Treatment of Glaucoma. The established lead that marihuana and more specifically tetrahydrocannabinol (THC) lowers intraocular pressure (IOP) in open-angle glaucoma but the side effects of THC and most of its studied synthetic derivatives limit or prevent their usage. This proposed program is to provide selected cannabinoids from the several classes that occur in Cannabis, screen the selected compounds for IOP lowering effects and to perform futher studies to develop the best cannabinoid for the treatment of open-angle glaucoma. The program involves the development of sources of supplies needed in pre-clinical animal studies and also for the clinical investigations. This proposal will provide suitable dosage form and supporting animal data for the clinical studies but not the clinical investigations per se. Within this program are planned studies of selected cannabinoids for their effects on aqueous humor dynamics and on ocular blood pressure and ocular blood flow. Effects of these compounds on systemic blood pressure and central nervous system function will be ascertained by general pharmacologic methodology and by injection into the third ventricle. The special ocular studies that are part of this program will be performed at the Glaucoma Center, Department of Ophthalmology, Washington University Medical School, St. Louis, Missouri. The collaborative work at the Glaucoma Center though part of the program is not part of the budget.